The major objective of the proposed research focuses on a better understanding of the etiology of protein folding. A two-prong attack will be attempted: improvements of secondary structure prediction technology and spatial comparisons of the three-dimensional architectures of proteins. The super-secondary structures to be investigated through superpositions, amino acid analyses, and packing arrangements include barrels, coiled helical aggregates, and face-to-face sheet domains. Common active site geometries and subunit interactions resulting from these secondary structure cluster will also be examined. The superposition and search technology essentially consists of a least-squares minimization of distances between equivalenced atoms and has been fully developed on theoretical and computerization levels. The secondary structure aspects of the investigation deal with the computerization and distribution of a joint prediction histogram, an assessment of present prediction techniques, and improvements in the prediction methodology. The significance of the research concerns the structure-function relationship in proteins, the raison d'etre of protein folding, essential features of catalysis, domain interactions, principles of molecular evolution, and common ion binding configurations.